Hepatic disease liver fibrosis

Liver Methotrexate causes hepatotoxicity, fibrosis, and cirrhosis, but generally only after prolonged use. Acutely, liver enzyme elevations are frequent, usually transient and asymptomatic, and also do not appear predictive of subsequent hepatic disease. Liver biopsy after sustained use often shows histologic changes, and fibrosis and cirrhosis have occurred these latter lesions often are not preceded by symptoms or abnormal liver function tests (see Precautions). For this reason, periodic liver biopsies are usually recommended for psoriatic patients who are under long-term treatment. Persistent abnormalities in liver function tests may precede appearance of fibrosis or cirrhosis in the RA population. 

The incidence of liver complications associated with PN ranges from approximately 7% to 84%, and end-stage liver disease develops in as many as 15% to 40% of adult patients on long-term PN.35 Patients often develop a mild increase in liver enzymes within 1 to 2 weeks of initiating PN, but this generally resolves when PN is discontinued. Severe liver complications include hepatic steatosis (fat deposition in liver), steatohepatitis (a severe form of liver disease characterized by hepatic inflammation that may progress rapidly to liver fibrosis and cirrhosis), cholestasis, and cholelithiasis.35... 

Steatohepatitis A severe form of liver disease caused by fat deposition in the liver, characterized by hepatic inflammation that may rapidly progress to liver fibrosis and cirrhosis. 

A 66-year-old woman with a pigmentary retinopathy that had been treated for 30 years with antocyanosides combined with beta-carotene (total dose 165 g) developed anicteric cholestasis. Liver biopsy showed pronounced portal fibrosis with normal bile ducts and no evidence of portal inflammation. The usual causes of chronic hepatic diseases were excluded. The serum concentration of vitamin A was 0.43 (reference range 0.5-0.8) mg/ml. After withdrawal of beta-carotene and administration of ursodeoxychohc acid for 6 months the cholestasis resolved. 

Stored ester reserves. It should be noted that there are reports indicating that continued dietary supplementation of alcoholic cirrhosis (Mobarhan et al.y 1981) or cystic fibrosis (Fulton et al, 1982) patients with vitamin A in high doses does not always cause a sustained rise in plasma levels, though it may correct abnormalities in dark adaptation. These findings indicate that in these subjects with diseased livers, an impaired RBP synthetic rate is a major contributing factor to low circulating levels of retinol. Furthermore, alcohol per se has been shown in baboons and rats to increase the rate at which retinol is catabolized by hepatic tissue (Sato and Lieber, 1981) and some data from rats suggest that alcohol may potentiate the sensitivity of tissues to vitamin A, even in the presence of normal blood levels (Leo and Lieber, 1982). 

CDG-Ib has been reported in at least 16 patients. It is a hepatic-intestinal disease with liver fibrosis and protein-losing enteropathy and can be associated with coagulation disturbances, hyperinsulinemic hypoglycemia and/or prolonged episodic vomiting [6-8]. 

Wilson s disease is another autosomal recessive disease leading to cirrhosis. Protein abnormalities result in excessive copper deposition in body tissues. The faulty protein is responsible for facilitating copper excretion in the bile, so copper accumulates in hepatic tissue. High copper levels within hepatocytes are toxic, and fibrosis and cirrhosis may develop in untreated patients. Those with Wilson s disease usually present with symptoms of liver or neurologic disease while still in their teens. 

Liver biopsy Mild inflammation and minimal fibrosis (grade 1, stage 1 disease) that is consistent with chronic hepatitis C... 

Hepatic Effects. Severe cirrhosis of the liver was one of the primary systemic effects seen following injection of Thorotrast in humans (Baxter et al. 1980a, b Faber 1979 Kato and Kido 1987 Kato et al. 1983 Mori et al. 1979, 1983a, b Rao et al. 1986 Van Kaick et al. 1983). Cases of fibrosis, veno-occlusive disease, and blood-filled cavities were also found in the livers of Thorotrast patients (da Silva Horta 1967a Dejgaard et al. 1984). The latency period for the appearance of the cirrhosis was not clear, but was probably comparable to the latency period for liver tumors (25-30 years) since the two effects were often found together. 

Portal hypertension most commonly occurs as a consequence of chronic liver disease. Portal hypertension Is caused by Increased blood flow within the portal venous system and increased resistance to portal flow within the liver. Splanchnic blood flow is increased in patients with cirrhosis due to low arteriolar resistance that is mediated by increased circulating vasodilators and decreased vascular sensitivity to vasoconstrictors. Intrahepatic vascular resistance is increased in cirrhosis due to fixed fibrosis within the spaces of Disse and hepatic veins as well as reversible vasoconstriction of hepatic sinusoids and venules. Among the consequences of portal hypertension are ascites, hepatic encephalopathy, and the development of portosystemic collaterals—especially gastric or esophageal varices. Varices can rupture, leading to massive upper gastrointestinal bleeding. 

Hepatitis C virus (HCV) was discovered in 1989 and has been regarded as the key causative agent for non-A, non-B virus hepatitis (33-35). It is estimated that there are over 170 million people worldwide and about 4 million individuals in United States with chronic HCV infection (36). Majority of the infected persons (80%) develop chronic hepatitis, where about 10-25% of them could advance to serious HCV-related liver diseases such as fibrosis, cirrhosis, and hepatocellular carcinoma (37). Only a fraction of patients respond to current FDA-approved standard therapy with a sustained viral load reduction (38), and many of them could not tolerate the treatment because of the various severe side effects (39). Therefore, HCV still represents an unmet medical need which requires discovery and development of more effective and well-tolerated therapies. 

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